Pigmentary Glaucoma
Author: Yaniv Barkana, MD; Chief Editor: Hampton Roy, Sr, MD
Pigment dispersion syndrome (PDS) is an autosomal dominant disorder characterized by disruption of the iris
pigment epithelium (IPE) and deposition of pigment granules on the structures of the anterior segment.
Pigment granule accumulation in the trabecular meshwork then leads to progressive trabecular dysfunction and
ocular hypertension with or without associated glaucomatous optic neuropathy. Because the age of onset is
often in the third or fourth decade of life, this disorder is an important and often underdiagnosed glaucoma
affecting younger people.
Pigmentary glaucoma (PG) originally was considered rare. In 1949, Sugar and Barbour described 2 young,
myopic men with Krukenberg spindles, hyperpigmented trabecular meshworks and open angles, whose
intraocular pressures (IOPs) increased with mydriasis and decreased with pilocarpine. [1] Investigations over the
ensuing decades elucidated further features, including bilaterality, association with myopia, and a greater
incidence in males.
Although primary open-angle glaucoma (POAG) usually begins after age 40 years, pigment dispersion
syndrome and pigmentary glaucoma typically affect younger individuals. The diagnosis of elevated IOP at a
young age should prompt the examiner to search for a cause.
Myopia is an important risk factor for the development of pigment dispersion syndrome and is present in
approximately 80% of affected individuals. Patients with higher degrees of myopia and deeper anterior
segments tend to develop glaucoma at an earlier age. In patients with asymmetric disease, the more affected
eye is usually the eye that is more myopic.
Pigment dispersion syndrome appears to be autosomal dominant with incomplete penetration, the phenotype
expression of which appears to be increased by the presence of myopia. Several pedigrees have been
described with multiple affected members, and at least one genetic locus on chromosome band 7q35 has been
identified.
Examples of pigmentary glaucomas are shown in the images below.
To record changes in the pigmentation of the iris,
the illumination beam must be directed coaxially through the pupil so that the retinal reflection appears in areas denuded of
pigment granules. This transillumination photograph shows the sectoral defects associated with pigmentary glaucoma.
Goniography uses diagnostic mirrored contact
lenses to overcome corneal refraction and to permit visualization of the filtration angle. The pigment liberated from the iris in
pigmentary glaucoma is shown in the angle, clogging the trabecular meshwork and impeding aqueous outflow.
Epidemiology
Frequency
United States
This condition is less common than open-angle glaucoma.
Mortality/Morbidity
If disease is not controlled, cupping of optic disk [4] and reduction of visual field can occur.
Race
Pigment dispersion glaucoma almost exclusively affects whites.
Sex
A higher incidence occurs in males.
Age
Onset usually occurs before age 40 years
History
Patients with pigmentary glaucoma (PG) are usually asymptomatic.
Pathophysiology
The classic triad of clinical signs of pigment dispersion syndrome consists of a Krukenberg spindle, slitlike,
radial, midperipheral iris transillumination defects, and pigment deposition on the trabecular meshwork. The iris
tends to have a concave configuration and often inserts into the posterior ciliary body band. [2, 3]
Liberated pigment granules are borne by aqueous currents and deposited on the structures of the anterior
segment. The vertical accumulation of these pigment granules along the corneal endothelium is known as a
Krukenberg spindle. The spindle tends to be slightly decentered inferiorly and wider at its base than its apex.
The spindle generally appears as a central, vertical, brown band up to 6 mm long and up to 3 mm wide. With
time, it becomes smaller and lighter and often requires careful examination to identify it.
Physical
Many patients with pigment dispersion glaucoma remain undetected, while those patients with glaucoma are
misdiagnosed more often than not as having juvenile-onset glaucoma or primary open-angle glaucoma
(POAG).[5] Those patients without elevated intraocular pressure (IOP) may have the presence of Krukenberg
spindles noted, but they often are told that they have normal eye examinations and are not cautioned regarding
possible future consequences of or the hereditary nature of the syndrome. Phenotypic expression varies, and
some manifestations may be extremely subtle or perhaps not expressed at all, leading to lack of detection in a
large segment of affected persons. Finally, many emmetropes and hyperopes, particularly prior to the onset of
presbyopia, never undergo formal eye examinations, and even less frequently are they examined by
ophthalmologists.
Movement of the posteriorly bowed concave iris along the anterior zonular fibers results in the
characteristic iris transillumination defects. This finding is pathognomonic for pigment dispersion syndrome
(PDS). Searching for iris transillumination defects prior to pupillary dilation using a small slit beam in a
darkened room is best. However, patients who do not appear to have transillumination defects on
retroillumination but have increased trabecular pigmentation, Krukenberg spindle, myopia, or juvenile openangle glaucoma can be examined with scleral transillumination using a fiberoptic scleral transilluminator in a
darkened room to facilitate detection. Infrared video pupillography is also useful to determine the extent of the
defects.[6]
Pigment accumulation on the anterior surface of the iris often appears as concentric rings within the
iris furrows. More diffuse pigmentation can cause a diffuse darkening of iris color, which is more apparent in
lightly pigmented irides because of the degree of color change. Asymmetric pigment liberation may result in
iris heterochromia, with the darker iris being the more affected side.
Pigment deposition in the trabecular meshwork typically produces a homogenous, densely pigmented
band (mascara line). In older patients, in whom the trabecular meshwork begins to recover and the pigment
gradually clears, the pigment band may become darker superiorly more than inferiorly, a pattern referred to
as the pigment reversal sign. In these patients, it may be the only sign that suggests previous pigment
dispersion. In such cases, examination of these patients' children may be confirmatory.
Pigment may also accumulate at the zonular attachments to the lens, where it may form a Zentmayer
ring.
Patients with pigment dispersion syndrome and pigmentary glaucoma are at increased risk for retinal
detachment, which may occur in as many as 6-7% of individuals. Retinal breaks and lattice degeneration may
occur twice as frequently in these eyes when compared to age and refraction-matched controls and are
independent of the use of miotics and degree of myopia.
Causes
As described by Campbell in 1979, mechanical contact between the concave posterior iris surface and anterior
zonular packets is responsible for the release of pigment granules from the iris pigment epithelium (IPE).
[7]
Histopathologic study and electron microscopy have confirmed the location of the iris defects to closely
correspond to the position of the zonular packets. Whether a defect of the iris pigment epithelium in pigment
dispersion syndrome contributes to their rupture or whether the release is due to mechanical forces alone is not
known.
Greater pigment liberation tends to occur in eyes with more pronounced iris concavity, presumably
because of the closer proximity of the iris pigment epithelium to the zonules. The insertion of the iris into the
ciliary body has been reported to be more posterior in pigment dispersion syndrome than in control eyes, an
anatomic variation which places the iris pigment epithelium into closer proximity to the zonular apparatus and
may increase the likelihood of iridozonular contact and zonular pigment dispersion. Trabecular endothelial
damage and meshwork dysfunction lead to elevated IOP in susceptible individuals.
Active pigment liberation typically occurs in patients in their third and fourth decades in life. As affected
individuals age, increased pupillary miosis and cataract formation cause a slow increase in relative pupillary
block, which increases resistance of aqueous flow from the posterior chamber, through the pupil, and into the
anterior chamber. This permits accumulation of aqueous within the posterior chamber and increases the
distance between the zonules and the iris. This may result in either a decrease or resolution of active pigment
release by decreasing iridozonular contact.
Continued phagocytosis of existing pigment in the trabecular meshwork may result in better aqueous
outflow, improving IOP control. Lichter and Shaffer observed a definite decrease in the amount of meshwork
pigment in 10% of 102 patients and concluded that the pigment could pass out of the meshwork as the
patient aged.[8] Older patients presenting with glaucoma may have only very subtle manifestations, if any, of
pigment dispersion syndrome, and may be diagnosed to have primary open-angle glaucoma or low-tension
glaucoma.
Reverse pupillary block involves the following:
Iridozonular contact occurs in pigment dispersion syndrome because the iris has a concave
configuration, which brings it into closer approximation to the zonular apparatus. Since iris position changes
with fluid pressure gradients within the anterior segment, the concept of reverse pupillary block has
developed to explain the anatomic abnormalities, which lead to the iris concavity.
In reverse pupillary block, aqueous humor pressure is greater in the anterior chamber than in
the posterior chamber. This is the opposite of relative pupillary block seen in angle-closure glaucoma, in
which resistance to aqueous flow through the pupil causes the iris to move anteriorly and close the angle.
Pupillary block angle-closure is relieved by laser iridectomy, which allows aqueous to move freely through
the iridectomy into the anterior chamber, relieving the pressure gradient across the iris and opening the
angle.
Reverse pupillary block could occur if an aliquot of aqueous were to be introduced suddenly
into the anterior chamber and then trapped there, so as to be unable to equilibrate with aqueous in the
posterior chamber. The increased pressure within the anterior chamber forces the iris against the lens,
creating a flap valve that maintains the pressure differential between the chambers by preventing
movement of aqueous back into the posterior chamber. The relative pressure difference between the 2
chambers would cause the iris to assume a concave configuration.
A concave iris configuration caused by a relative pressure differential between the anterior
and posterior chambers is not unique to pigment dispersion syndrome. In iris retraction syndrome,
increased uveoscleral outflow facilitated by retinal pigment epitheliumassisted fluid absorption in the
presence of a retinal break causes the pressure within the posterior segment and the posterior chamber to
be less than that of the anterior chamber. Eyes with iris retraction syndrome have extensive posterior
synechiae preventing free flow of anterior chamber fluid into the posterior chamber.
During routine phacoemulsification, posterior movement of the lens-iris diaphragm during the
irrigation at the time of insertion of the phacoemulsification handpiece may be in part caused by a rapid
increase in anterior chamber volume, which forces the iris against the lens surface. Because of this flapvalve effect, fluid cannot move into the posterior chamber, and the entire lens-iris diaphragm may move
posteriorly.
Lid blinking may have a prominent contributory influence on iris configuration, and, thus, on the
distribution of aqueous humor in the anterior segment.
In 1994, Chew proposed that a blink initially deforms the cornea, transiently increasing IOP (in
both the anterior and posterior chambers), and pushes the iris posteriorly against the lens. [9] Immediately
following the blink, pressure within the posterior chamber exceeds that of the anterior chamber and a small
aliquot of aqueous moves into the anterior chamber along this pressure gradient. This causes the anterior
chamber pressure to exceed that of the posterior chamber for a brief period. This momentary pressure
gradient causes the iris to become concave and push it against the lens, preventing aqueous from flowing
back into the posterior chamber (reverse pupillary block). The presence of cornea deformation during
blinking has been reported in animal studies.
o
Increased iridolenticular contact and myopia, both present in pigment dispersion syndrome,
appear to enhance the flap-valve effect of iris-lens contact, which helps to prevent equilibration of pressure
between the 2 chambers. In nonpigment dispersion syndrome eyes, this reverse pupillary block
mechanism is less complete and less able to maintain the pressure differential.
o
When blinking is prevented, aqueous secretion gradually increases the volume of the
posterior chamber. As the volume and the pressure of the posterior chamber increase relative to the
anterior chamber, the iris gradually flattens, iridolenticular contact diminishes, and iridozonular and
iridociliary process distances increase.
A concave iris configuration indistinguishable from that associated with pigment dispersion syndrome
can be induced by accommodation in young, healthy individuals. During accommodation, contraction of the
ciliary ring causes the lens to move forward slightly, which shallows the anterior chamber. The displaced
aqueous cannot move into the posterior chamber because of the flap-valve effect; therefore, it is forced into
the angle recess. Aqueous humor, now trapped in the anterior chamber, is forced into the angle recess and
the peripheral iris assumes a concave configuration. This process is similar to the change in iris and angle
configuration, which occurs during indentation gonioscopy.
Pharmacologic pupillary dilation may result in marked pigment liberation accompanied by a rise in IOP.
The same phenomenon may occur in some patients with pigment dispersion syndrome during strenuous
exercise, particularly exercise involving jarring movements, such as jogging or basketball. Pretreatment with
low-dose pilocarpine prior to exercise can limit both the pigment liberation and the IOP spike. Laser
iridectomy (see Surgical Care) may not completely eliminate exercise-induced pigment liberation.
o
Diagnostic Considerations
Pigment dispersion syndrome (PDS) can usually be easily distinguished from most other abnormalities in which
dissemination of pigment is part of the disease process because no other condition that results in the
characteristic iris transillumination defects is known. Other disorders associated with signs of pigment
dispersion in the disruption of melanoma cells (eg, melanomalytic dispersion), cysts of the iris and ciliary body,
postoperative conditions (eg, intraocular lensiris chafing), and exfoliation syndrome often occur unilaterally.
An increase of pigment dispersion syndrome and pigmentary glaucoma (PG) secondary to iris chafing by
intraocular lenses that were implanted in the ciliary sulcus, leading to the removal of the lens and/or
trabeculectomy in some cases, has been reported. [10] Phakic intraocular lenses can also result in pigment
dispersion syndrome and pigmentary glaucoma. In these conditions, trabecular pigmentation is often less
dense and is usually unevenly distributed throughout the circumference of the meshwork. Occasionally,
pigment granules in the anterior chamber may be confused with inflammatory cells, leading to a misdiagnosis
of uveitis.[11]
The disease process most similar to pigmentary glaucoma is exfoliation glaucoma. In this condition, a loss of
pigment occurs from the iris pigment epithelium (IPE), iris transillumination, pigment dispersion in the anterior
segment, including Krukenberg spindle, trabecular pigmentation, and intraocular pressure (IOP) elevation. The
clinical history combined with a careful slit lamp biomicroscopic examination easily separates the 2 diseases.
The age of onset for exfoliation glaucoma is usually older than 60 years, and onset is rare in persons younger
than 40 years. No sexual or racial predilection exists for exfoliation syndrome, although reports seem to
indicate a higher prevalence of the disease in individuals of Scandinavian ancestry.
Meshwork pigmentation in exfoliation glaucoma is not as intense as in pigmentary glaucoma. Iris
transillumination characteristically begins at the pupillary border and not the midperiphery. Unlike pigment
dispersion syndrome, approximately 50% of patients with exfoliation syndrome are affected clinically in only
one eye. Finally, the presence of white flakes of exfoliation material at the pupillary border and on the anterior
lens surface is diagnostic of exfoliation syndrome.
Other factors to consider include the following:
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Pigmentation of trabecular network
Elderly individuals (inferior nasal or faint band circumstantial)
Pseudoexfoliation of lens with or without glaucoma (unilateral or bilateral)
Pigmentary glaucoma
Krukenberg spindle without glaucoma
Malignant melanoma (1 eye)
Cyst of pigment layer or iris (unilateral)
Previous intraocular operation, inflammation, or hyphema (scattered, mostly in lower angle)
Nevus (dense, isolated patch)
Open-angle glaucoma (patchy band, whole circumference)
Following glaucoma irradiation for malignancy of nasal sinus
Pigment liberation into anterior chamber with dilation of pupil
Diabetes mellitus (Willis disease)
Exercise
Hurler disease (mucopolysaccharidoses type IH)
Low-tension glaucoma with pigment dispersion
Retrocorneal pigmentation
Endothelial phagocytosis of free melanin pigment as Krukenberg spindle
Iris melanocytes, iris pigment epithelial cells, or pigment-containing macrophages in the
posterior corneal surface can follow operative or accidental ocular trauma
Status posthyphema
Differential Diagnoses
Angle Recession Glaucoma
Aphakic and Pseudophakic Glaucoma
Drug-Induced Glaucoma
Juvenile Glaucoma
Plateau Iris Glaucoma
Primary Open-Angle Glaucoma
Imaging Studies
See the list below:
Ultrasound biomicroscopy (UBM) has been particularly useful in evaluating the structures surrounding
the posterior chamber in patients with pigmentary glaucoma (PG).[12] UBM shows the posterior iris insertion,
[13]
iris concavity, iridozonular contact, and extensive iridolenticular contact.
Slit-lamp optical coherence tomography has been used to assess the parameters of the anterior
chamber and angle dimensions in patients with pigmentary glaucoma. [14, 15]
Medical Care
Although many individuals have pigment dispersion syndrome (PDS), fewer than one half will develop ocular
hypertension or glaucoma. However, because pigment dispersion syndrome is a risk factor for the development
of ocular hypertension, all patients with this disorder should undergo periodic eye examinations. This is
particularly important during the pigment liberation phase of the disease. The frequency of follow-up care can
be decreased when pigment liberation ceases or trabecular pigmentation begins to diminish.
Pigment dispersion syndrome is typically a bilateral disease, although asymmetry may occur. A
correlation is noted between the amount of pigment lost from the posterior surface of the iris, increased
degree of pigmentation in the trabecular meshwork, and degree of dysfunction in the trabecular meshwork as
evidenced by elevation of the intraocular pressure (IOP). The size and density of the Krukenberg spindle
does not necessarily correlate with trabecular meshwork damage. However, the amount of pigment that is
presented to the trabecular meshwork does play a role in the elevation of the IOP. Markedly asymmetric
disease is usually due to an additional factor, making one eye worse, such as anisometropia or the
development of exfoliation syndrome or angle recession, or an additional factor acting to prevent the
development of pigment dispersion syndrome, such as aphakia or Horner syndrome.
Progressive glaucomatous optic neuropathy in pigmentary glaucoma (PG) is primarily pressure
dependent and reduction of IOP is the mainstay of therapy. In addition to monitoring of IOP, sequential
ophthalmic examinations should include gonioscopy to assess the degree and progression of trabecular
pigmentation, stereoscopic evaluation and photography of the optic nerve, and perimetry.
Because the degree and stage of pigment liberation, IOP, and extent of glaucomatous optic
neuropathy vary among individuals, each must be evaluated to determine the proper course of intervention.
As understanding of the pathogenesis of pigment liberation expands, consideration also should be given to
gearing therapy toward eliminating acute pigment release, rather than just treating elevated IOP.
The mainstay of initial medical therapy for pigmentary glaucoma continues to be aqueous suppression
with a topic beta-blocker, primarily because of the relatively easy dosing schedule and minimal side effects.
Parasympathomimetics may also be administered.
o
In theory, therapy directed at increasing relative pupillary block should relieve iridozonular
contact and diminish pigment liberation. The relief of iridozonular contact following miotic therapy has been
demonstrated with ultrasound biomicroscopy (UBM). Pupillary miosis increases resistance to aqueous flow
from the posterior chamber, past the lens surface, and through the pupil into the anterior chamber. This
increased resistance allows aqueous pressure to build within the posterior chamber (ie, relative pupillary
block), and forces the iris to move anteriorly, away from the zonules, and assume a convex configuration.
However, strong miotics in young individuals rarely are tolerated because of the associated spasm of
accommodation and blurring of vision.
o
Low-dose pilocarpine, in the form of Ocusert, often provides enough miosis to create pupillary
block, without disabling adverse effects. A careful peripheral retinal examination should be performed before
and after the institution of or change in miotic therapy because of the higher incidence of retinal breaks and
detachment in these patients.
Alpha-agonists are useful in pigmentary glaucoma, but the development of allergy in as many as 50%
of patients precludes the long-term use of dipivefrin, epinephrine, and apraclonidine in many individuals.
Brimonidine tartrate 0.2% may provide satisfactory IOP with less allergic reaction than other drugs in this
class.
Topical carbonic anhydrase inhibitors are useful agents for treating pigmentary glaucoma and are
generally well tolerated. Systemic agents should be reserved for particularly difficult circumstances or when
the risks of surgery are unacceptably high.
Prostaglandin analogues, which lower IOP by increasing uveoscleral outflow are effective in treating
pigmentary glaucoma and offer the advantage of once daily administration. The iris surface color change that
may occur during therapy appears to involve increased melanin production by iris melanocytes and is not
known to affect the iris pigment epithelium (IPE) or result in pigment dispersion.
Surgical Care
See the list below:
Laser trabeculoplasty: Argon laser trabeculoplasty may be offered as a treatment in the management
of uncontrolled pigmentary glaucoma. Although the initial result is often good, a larger proportion of patients
can lose control of IOP when compared to patients with primary open-angle glaucoma (POAG), and the loss
of control can occur in less time. In contrast to other forms of open-angle glaucoma, younger patients appear
to respond better to trabeculoplasty than older individuals. Selective laser trabeculoplasty has been reported
to result in marked and sustained IOP elevation, necessitating trabeculectomy in a few eyes with pigmentary
glaucoma; therefore, it should be used with great caution. [16]
Laser iridectomy: Laser iridectomy eliminates the iris concavity present in most patients with pigment
dispersion syndrome by permitting equalization of pressures between the anterior and posterior chambers.
This causes the iris to become flat, thereby decreasing iridozonular contact and reversing the underlying
anatomical defect, which results in pigment dispersion. Anecdotal evidence suggests that this can prevent
continued pigment liberation, result in a reversal of trabecular pigmentation, and, subsequently, lower IOP.
However, long-term lowering of IOP and stabilization of glaucomatous optic neuropathy and visual field loss
have not been demonstrated conclusively. Although theoretically sound, laser iridectomy should be used with
caution because of the paucity of data regarding the long-term efficacy of this procedure.
Filtering surgery: The surgical management of patients with pigmentary glaucoma follows the same
principles and considerations used in the management of primary open-angle glaucoma. The appearance
and change in the optic nerve along with visual field defects should be the principal guidelines used in
deciding whether surgery is needed. Most patients respond well to standard filtration operations, although
antifibrosis agents may be indicated to achieve a low target pressure or for reoperation. No unusual problems
are typically encountered during cataract surgery.
Medication Summary
Despite the fact that glaucoma is not simply a disease of elevated intraocular pressure (IOP), current medical
therapy is directed toward lowering IOP.
A rational approach to choosing antiglaucoma medication should minimize the number of medications and
probability of significant adverse effects.
As mechanisms of axonal death by apoptosis become better understood, therapies may be developed to
protect nerve fibers from ongoing damage and death. This has been termed neuroprotection.
Agents currently under investigation as neuroprotective include the following: glutamate receptor blockers,
calcium channel blockers, inhibitors of nitric oxide synthase, free radical scavengers, and drugs to increase
blood flow to the optic nerve.
Bimatoprost (Lumigan), travoprost (Travatan), and unoprostone (Rescula) are new ophthalmic prostaglandin
analogs recently approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive
activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost and
unoprostone are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. They are selective FP
prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for
the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other
IOP-lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple
measurements over time) to another IOP-lowering medication.
Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs);
whereas, unoprostone must be administered bid. They have not been studied in pediatric patients.
These medications are contraindicated if hypersensitivity has been documented. No drug interactions have
been reported. All are classified as pregnancy category C (ie, safety for use during pregnancy has not been
established).
Like latanoprost, all demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie,
increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use
is cautioned in uveitis or macular edema. They should not be used if inflammation is present.
Further Outpatient Care
See the list below:
Long-term monitoring of pigmentary glaucoma (PG) is important to assess the effectiveness of the
therapy.
Complications
See the list below:
Long-term follow-up care is needed for patients with glaucoma to ensure control of the disease.
Prognosis
See the list below:
Prognosis is favorable with control of intraocular pressure (IOP
Patient Education
See the list below:
Good patient education helps to ensure compliance with the treatment of this chronic disorder.
For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see
eMedicineHealth's patient education article Ocular Hypertension, Glaucoma Overview, Glaucoma FAQs,
and Glaucoma Medications.
